All sectors of the human cerebral cortex receive dense cholinergic input. T
he origin of this projection is located in the Ch4 cell group of the nucleu
s basalis of Meynert, However, very little is known about the location of t
he pathways which link the cholinergic neurons of the nucleus basalis to th
e human cerebral cortex. This question was addressed in whole-hemisphere se
ctions processed for the visualization of multiple cholinergic markers. Two
highly organized and discrete bundles of cholinergic fibres extended from
the nucleus basalis to the cerebral cortex and amygdala and were designated
as the medial and lateral cholinergic pathways. These bundles contained ac
etylcholinesterase, choline acetyltransferase and nerve growth factor recep
tors, confirming their cholinergic nature and origin within the basal foreb
rain, The medial pathway joined the white matter of the gyrus rectus, curve
d around the rostrum of the corpus callosum to enter the cingulum and merge
d with fibres of the lateral pathway within the occipital lobe, It supplied
the parolfactory, cingulate, pericingulate and retrosplenial cortices, The
lateral pathway was subdivided into a capsular division travelling in the
white matter of the external capsule and uncinate fasciculus and a perisylv
ian division travelling within the claustrum, Branches of the perisylvian d
ivision supplied the frontoparietal operculum, insula and superior temporal
gyrus, Branches of the capsular division innervated the remaining parts of
the frontal, parietal and temporal neocortex, Representation of these chol
inergic pathways within a 3D MRI volume helped to identify white matter les
ion sites that could interfere with the corticopetal flow of cholinergic pa
thways.